Selective lysis of erythrocytes infected with the trophozoite stage of Plasmodium falciparum by polyene macrolide antibiotics

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dc.contributor.authorWiehart U.I.M.
dc.contributor.authorRautenbach, Marina
dc.contributor.authorHoppe H.C.
dc.date.accessioned2011-05-15T16:01:17Z
dc.date.available2011-05-15T16:01:17Z
dc.date.issued2006
dc.description.abstractThe continuous increase in strains of the human malaria parasite Plasmodium falciparum resistant to most front-line antimalarial compounds is reason for grave clinical concern. The search for new drugs led us to investigate a number of membrane active polyene macrolide antibiotics, such as amphotericin B, nystatin, filipin and natamycin. The interaction of these compounds with sterols in bilayer cell membranes can lead to cell damage and ultimately cell lysis. The malaria parasite modifies the host erythrocyte membrane by changing the protein and lipid composition and thus the infected cell could be a selective target for membrane active compounds. We found that erythrocytes infected with the trophozoite stage of P. falciparum were particularly susceptible to lysis by amphotericin B (Fungizone™) and, to a lesser extent, nystatin, as determined by ELISA and various microscopy assays. Liposomal amphotericin B (AmBisome™) displayed a similar specificity for parasitised erythrocytes, but complete lysis required a longer incubation period. In contrast, filipin and natamycin did not distinguish between normal and parasite-infected erythrocytes, but lysed both at similar concentrations. In addition, when added to ring-stage cultures, the amphotericin B preparations and nystatin produced a marked disruption in parasite morphology in less than 2 h without an accompanying permeabilisation of the infected host cell, suggesting a second plasmodicidal mode of action. The results imply that selected polyene macrolide antibiotics or their derivatives could find application in the treatment of severe malaria caused by of P. falciparum. © 2006 Elsevier Inc. All rights reserved.
dc.description.versionArticle
dc.identifier.citationBiochemical Pharmacology
dc.identifier.citation71
dc.identifier.citation6
dc.identifier.issn62952
dc.identifier.other10.1016/j.bcp.2005.12.012
dc.identifier.urihttp://hdl.handle.net/10019.1/11900
dc.subjectamphotericin B deoxycholate
dc.subjectamphotericin B derivative
dc.subjectamphotericin B lipid complex
dc.subjectfilipin
dc.subjectmacrolide
dc.subjectnatamycin
dc.subjectnystatin
dc.subjectpolyene antibiotic agent
dc.subjectsterol
dc.subjectanimal cell
dc.subjectantibiotic sensitivity
dc.subjectarticle
dc.subjectbilayer membrane
dc.subjectcell culture
dc.subjectcell membrane permeability
dc.subjectconcentration (parameters)
dc.subjectcontrolled study
dc.subjectdrug mechanism
dc.subjectdrug targeting
dc.subjectenzyme linked immunosorbent assay
dc.subjecterythrocyte fragility
dc.subjecterythrocyte membrane
dc.subjecterythrocyte parameters
dc.subjecterythrocyte structure
dc.subjecthemolysis
dc.subjecthost cell
dc.subjectincubation time
dc.subjectlipid composition
dc.subjectmalaria falciparum
dc.subjectmicroscopy
dc.subjectnonhuman
dc.subjectPlasmodium falciparum
dc.subjectpriority journal
dc.subjectprotein targeting
dc.subjecttrophozoite
dc.subjectAmphotericin B
dc.subjectAnimals
dc.subjectAnti-Bacterial Agents
dc.subjectAntiprotozoal Agents
dc.subjectDose-Response Relationship, Drug
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectErythrocyte Membrane
dc.subjectErythrocytes
dc.subjectFilipin
dc.subjectHemolysis
dc.subjectHumans
dc.subjectLife Cycle Stages
dc.subjectNatamycin
dc.subjectNystatin
dc.subjectPlasmodium falciparum
dc.titleSelective lysis of erythrocytes infected with the trophozoite stage of Plasmodium falciparum by polyene macrolide antibiotics
dc.typeArticle
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